A new study suggests that ancient viral DNA sequences are active in the brains of modern humans and actually contribute to the risk of mental disorders.
Human Genomic Fossils
About 8% of the human genome is composed of sequences called Human Endogenous Retroviruses (HERVs), which came from ancient viral infections that took place hundreds of thousands of years ago. They resulted from the integration of exogenous retroviruses into the germ cells of our mammalian ancestors.
Most HERVs have become silenced due to mutations like insertions, substitutions, deletions, or epigenetic changes. Experts previously thought that these "fossil viruses" were just junk DNA with no important function in our bodies.
Advances in genomics research, however, have allowed scientists to identify the location of these fossil viruses in our DNA. Recent technological breakthroughs also enabled them to better understand when fossil viruses are expressed and what particular functions they may actually have.
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Ancient Viruses and Mental Health
At King's College London, scientists discovered that thousands of DNA sequences coming from ancient viral infections are expressed in our brain, with some playing a vital role in a person's susceptibility to depression, bipolar disorder, and schizophrenia. The details of the study are discussed in the paper "Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions."
Led by Dr. Timothy Powell from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), the research team used a novel and robust approach to assess how genetic vulnerability for mental disorders relays its effects on the expression of ancient viral sequences found in the genome of modern humans.
The researchers investigated data from large genetic studies involving tens of thousands of people both with and without mental health conditions. They also used information from autopsy brain samples from 800 participants in order to understand how DNA variations associated with psychiatric disorders influence the expression of HERVs.
The result of their study suggests that these viral sequences likely play a more vital role in the human brain than previously thought, with specific HERV expression profiles being linked to an increased risk for some psychiatric disorders. Powell and colleagues found that some genetic risk variants affected the expression of HERVs, although most genetic risk variants associated with psychiatric diagnoses influenced genes with well-known biological functions.
The research team reported five robust HERV expression signatures linked with psychiatric disorders. These include one HERV associated with susceptibility to depression, two linked with risk for schizophrenia, and one associated with risk for both schizophrenia and bipolar disorder.
While it is still not yet clear how the HERVs influence brain cells to confer this susceptibility, the findings of the study suggest that the regulation of their expression is vital for brain function. For this reason, further studies are needed to understand the specific function of most HERVs, including those identified in this research.
According to research co-senior author Dr. Douglas Nixon, a better understanding of these retroviruses and the genes implicated in mental disorders have the potential to revolutionize mental health research. The new insights gathered from this study can also lead to novel ways of treating or diagnosing psychiatric disorders.
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